REGULATION OF ALTERNATIVE SPLICING IN-VIVO BY OVEREXPRESSION OF ANTAGONISTIC SPLICING FACTORS

The opposing effects of SF2/ASF and heterogeneous nuclear ribonucleopr otein (hnRNP) A1 influence alternative splicing in vitro. SF2/ASF or h nRNP A1 complementary DNAs were transiently overexpressed in HeLa cell s, and the effect on alternative splicing of several cotransfected rep orter genes was measured. Increased expression of SF2/ASF activated pr oximal 5' splice sites, promoted inclusion of a neuron-specific exon, and prevented abnormal exon skipping. Increased expression of hnRNP A1 activated distal 5' splice sites. Therefore, variations in the intrac ellular levels of antagonistic splicing factors influence different mo des of alternative splicing in vivo and may be a natural mechanism for tissue-specific or developmental regulation of gene expression.